Is LIPT2 p.Pro230= (c.690C>T) pathogenic?

LIPT2 p.Pro230= (c.690C>T) is classified Benign/Likely benign in LIPT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 5.96%, amr) — too common for a highly-penetrant pathogenic allele; Associated with encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities.

LIPT2 p.Pro230=

Q: What condition is associated with LIPT2 p.Pro230= (c.690C>T)?

LIPT2 p.Pro230= (c.690C>T) is associated with encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (ClinVar).

Q: How common is LIPT2 p.Pro230= (c.690C>T) in the general population?

LIPT2 p.Pro230= (c.690C>T) is common (popmax 5.96%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.690C>T · rs147957229 · VCV771448

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.96%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3.1, phastCons 0.98
Overall
CADD	2.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.96% Admixed American · 3,039/50,996 alleles

Filtering AF 5.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.71%

Overall 0.225% 3,492/1,550,706 alleles · common exomes 2,780/1,398,488 · genomes 712/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.96%	17
East Asian	0.357%	280
Remaining individualsnot grpmax-eligible	0.188%	532
African / African-American	0.137%	731
South Asian	0.0345%	2,898
European (non-Finnish)	0.00567%	17,633

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LIPT2
Protein: p.Pro230=
Coding: c.690C>T
MANE Select: NM_001144869
dbSNP: rs147957229
Type: single nucleotide variant
Location: chr11:74492141 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37

Full LIPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIPT2 p.Gly109Asp Uncertain significance ★★ ⚠ same condition
LIPT2 p.Gly95Asp Uncertain significance ★★ ⚠ same condition
LIPT2 p.Ile36Thr Uncertain significance ★★ ⚠ same condition
LIPT2 c.466+14A>C Benign ★★ same condition
LIPT2 p.Leu8= Benign ★★ same condition
LIPT2 p.Phe91= Benign/Likely benign ★★ same condition
LIPT2 p.Thr190Ser Benign ★★ same condition
LIPT2 p.Met1Leu Likely pathogenic ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lipt2-p-pro230 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown